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Keywords:

  • anti-IgE;
  • immunotherapy;
  • mastocytosis;
  • omalizumab;
  • venom

In a previous AllergyNet communication the control of recurrent reactions to venom immunotherapy (VImRx) in mastocytosis with high omalizumab dose was presented (1).

In brief, an adult male with underlying indolent systemic mastocytosis was subjected to VImRx for a near fatal anaphylactic reaction to a bee sting; adverse reactions occurred at a high rate throughout the 18 months of attempted VImRx. Omalizumab pretreatment (300 mg, twice the recommended dose) completely eliminated VImRx reactions. The two therapies were eventually administered on the same day, 40–60 min apart. Serial tryptase measurements – drawn just prior to the combined treatment – showed progressive reduction from 41.7 to 23 μg/l (Phase I, Fig. 1).

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Figure 1.  Time course of combined omalizumab pretreatment and bee venom immunotherapy and adverse reactions to the latter, plus serum tryptase levels in an adult patient suffering from indolent systemic mastocytosis.

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Encouraged by patient’s good response and by relevant reports published in the meantime (2–5), we decided to reduce the monthly omalizumab dose to 150 mg. This amount was administered every 30 days (course 9th through 11th) 40–60 min prior to the maintenance VImRx (Phase II, Fig. 1). An i.v. route was maintained with N.S. and vital signs were monitored (portable DASH 2000 monitor; GE Medical Systems IT Inc., Buckinghamshire, UK) under the continuous attendance of an allergologist.

The morning of 11th course, blood was drawn for tryptase determination (ImmunoCAP, Phadia, Uppsala, Sweden). Patient received the third, 150 mg, omalizumab dose and 40 min later 100 μg bee-venom; generalized facial flushing extending to the neck and chest area was noted after 25 min; he remained asymptomatic, but the monitor displayed mild tachycardia (up to 108, previous pulse rate 76–84); the rate of i.v. fluids was maximally increased. BP remained stable; pulse rate normalized after 15 min. A local reaction (30 × 35 mm wheal, 70 × 80 mm flare) developed at the venom injection site in 20 min; residual flushing and the cutaneous reaction were still present beyond one hour. Tryptase showed mild increase compared to the levels prior to reducing omalizumab (Fig. 1, Phase II).

Thereafter, anti-IgE dose was increased to 300 mg and patient remained completely free of any adverse effect. The morning of course No. 13th venom skin tests were performed and were positive again (10 × 13 mmW, 20 × 47F, at 1 μg/ml) for the first time since Omalizumab treatment had been initiated; tryptase – measured on that morning – showed continuous mild increase (Fig. 1).

Subsequently, for financial and convenience reasons, a gradual increase in the course interval was attempted; upon reaching 35 days (17th course) patient developed facial flushing (no subjective sensation) 20 min post-VimRx; flare without wheal, was noted at the venom injection site. The combined treatment schedule was again changed to 30-day intervals and has been continued uneventfully thereafter (courses No. 24–26) on an outpatient basis. ID venom-Skin tests performed during the latest session were negative up to the concentration of 1 μg/ml. Tryptase, drawn 2 weeks later, dropped to 18.3 mcg (Fig. 1, Phase II).

In conclusion, the present case-study on the protective effect of omalizumab in systemic mastocytosis undergoing VImRx, suggests that the beneficial effect appears to require higher than the recommended omalizumab dose and strictly 30-day administration intervals; the occurrence of mild cutaneous and cardiovascular signs, the immediate local reaction at the venom injection site and the conversion to skin test positivity, observed upon either omalizumab’s dose reduction or increased treatment-interval, suggest that no immunologic changes have occurred because of VImRx.

It appears logical to speculate that the excellent response noted during Phase I of this study is exclusively due to omalizumab’s mast cell stabilizing and probably other actions (5, 6); the changes noted in serum tryptase are in agreement. Obviously, this concept questions the logic of continuing VImRx. However, no valid conclusions can be drawn from a single case and the present findings need to be confirmed; because of the low systemic mastocytosis with venom anaphylaxis prevalence, a multicenter-study would be appropriate.

No financial or other relations with the manufacturing company of either drug used in this case study.

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